It is known that esters of certain steroids with alkanoic acids containing a phenyl group substituted with a bis(2-chloroethyl)amino group have antitumour activities in animals and human beings. The acid part of such known esters has in the main been 4-/N,N-bis(2-chloroethyl)amino/phenylacetic acid and 4-/4-(N,N-bis(2-chloroethyl)amino)phenyl/butanoic acid.
The types of steroids which have been investigated are estrogens, androgens, corticoids, and one sterol, cholesterol. The hydroxy group or groups in these steroids which have been esterified have been situated in one or two of the positions 3-(estrogens), 3.beta.-(androgens, pregnenolone, and cholesterol), 17.beta.-(estrogens and androgens) and 21-(corticosteroids).
Such esters are described in e.g. J. Med. Chem. 11 (1968) 1106, ibid 12 (1969) 810, ibid 15 (1972) 1158, and U.S. Pat. No. 3,732,260.
No esters of gestogens are known which in their acid part contain an alkylating group such as the bis(2-chloroethyl)amino group, although numerous gestogens are known which contain esterifiable hydroxy groups in various positions of the steroid molecules, e.g., at the 3, 11, 16, and 17-positions, much less are any such gestogen esters known in which the esterification is at the position of particular interest to the present invention, namely in the 17.alpha.-position.
It has now, surprisingly, been found that the esters of the present invention being 17.alpha.-esters of gestogens are active against animal tumours, and that they also show a very low toxicity resulting in very favouralbe therapeutic indexes.
The esters of this invention are of value in the treatment of tumours, for instance, in uro-genital organs, such as the ovaries, the endometrium, the prostate, the bladder, and the kidneys. The compounds are particularly useful in the treatment of tumours situated in organs which are targets for gestogens, such as the endometrium and the mammary glands. The compounds of the invention are also valuable in the treatment of haematological disorders.